Skeletal muscle adapts to a novel bout of strenuous exercise with a period of degeneration followed by a period of regeneration. Following overexertion exercise, these processes manifest themselves as prolonged losses in muscle function, loss of sarcolemmal integrity, muscle pain and soreness and inflammation. These indices of damage are profoundly attenuated when a second bout of exercise is performed up to 6 months after the first bout. While this "repeated bout effect" is well documented, the molecular mechanisms underlying this adaptation have not been identified. The primary aim of this research proposal is to detail gene expression changes following a repeated exercise bout of exercise in the human vastus lateralis of research subjects. Microarray analyses of muscle biopsy tissue will be used to provide a pattern of global gene expression at 6 hours after a first and second bout of exercise, providing concurrent information concerning how thousands of genes respond to damaging stimuli before and after the muscle has been given a chance to adapt to the stimuli. Microarray results for a subset of differentially regulated genes will be confirmed via qRT-PCR and localized via immunocytochemistry. These data will provide information concerning which genes underlie muscle damage and adaptation. The long-term objective of this study is to create a molecular map of the genes involved in muscle damage and adaptation. One of the most germane applications of this knowledge would be to the field of muscular dystrophy research, as muscular dystrophy patients undergo periods of muscle damage followed by failed regeneration. Understanding these processes could lead to novel treatments for musculodystrophy and other myopathies that are characterized by muscle degradation.